Teeth are mainly composed of enamel, dentin, and pulp chamber rich with nerves and blood vessels. Enamel and dentin are highly calcified hard tissue because of the component, hydroxyapatite (HAp). However, if they are stayed in an acidic environment for a period of time, they will lose mineral and become soft by the erosion of acid. After a prolonged time, the etching will decay teeth and dental caries will occur. Dental caries is a multifactor disease and concerns oral health.
Teeth may be damaged by acidic metabolites etching the dental surface, which causes loss of mineral substance and formation of caves on the enamel, and penetrating into the dentin or further into the pulp chamber. Acidic metabolites can be produced by food residue (such as carbohydrate) in the mouth. In addition, the decrease of saliva with age, the side effects of medication (such as anti-depression drug), or the deterioration of physical conditions will also reduce the oral buffering capacity, resulting in the decrease of the pH level and the formation of an acidic oral environment. As a result, the chance to get dental caries is largely increased.
In the oral environment, the phosphates and calcium ions in the liquid phase (saliva) and the solid phase (enamel) maintain a dynamic equilibrium between demineralization and remineralization. The equilibrium may be imbalanced by various factors, which leads to an increase of demineralization. Therefore, teeth can be repaired and caries can be prevented or alleviated so as to avoid pain or tooth loss by inhibiting the oral bacterial growth or buffer the acidity caused by soft drinks or bacteria metabolism.
Various product additives such as xylitol and fluoride were known in the prior art to diminish caries. Xylitol can inhibit bacteria growth, thereby decreasing oral acidity, and fluoride can increase anti-acidity of teeth. Although the above-mentioned additives can decelerate demineralization so as to prevent caries, these components cannot strengthen teeth directly. In addition, fluoride cannot sustain in oral for long time and can be lost due to saliva flow, thus limiting the benefit.
According to the dynamic equilibrium mechanism, remineralization can be improved by the increase of the concentration of phosphate ions and calcium ions in the oral environment. Among various calcium phosphate salts, amorphous calcium phosphate (ACP) is considered as an ideal source of calcium ions and phosphate ions because of its advantageous solubility. However, the solubility of ACP decreases after contacting water in a physiological environment as it transforms into crystalline hydroxyapatite (Ca10(PO4)6(OH)2). Furthermore, ACP only remains in mouth or dental surface for a short period, so its effect is difficult to be fully released. In 2004, Eric Reynolds of the University of Melbourne, Australia, used peptide fragments produced from enzyme-cleaved casein as carriers to chelate with ACP to form casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP) and constitute a core-shell structure to stabilize the amorphous structure of ACP and prevent ACP from transforming into crystalline calcium phosphate. The complex maintains solubility of ACP, attaches ACP to oral surfaces in a more secure way, keeps ACP for a longer time and extends its efficacy in preventing caries. Although CPP-ACP is effective in preventing caries, its popularity is limited because of the milk protein allergy among subjects, which is triggered by casein.
Therefore, the prior art on oral compositions attempting to solve the above-mentioned problems is extensive.
Taiwan Patent Publication No. 200600111 discloses a dental whitening method, comprising separately applying a whitening composition to the dental surface, wherein the whitening composition comprises at least one of oral acceptable peroxide, and introducing a micronized active composition in a volume of at most 2.5 ml to the surface. The reference discloses that the steps of applying the whitening composition and introducing the active composition are performed separately. In addition, the application mentions γ-polyglutamic acid as one of the options for controlling calculus, calcium glycerol phosphate as one of the options for controlling dental plaque, and calcium phosphate as one of the abrasives. It does not, however, mention the combination of γ-PGA and calcium phosphate and the effects that it may produce.
Taiwan Patent Publication No. 200600112 discloses a kit used in oral care, comprising (a) a composition, including an oral treatment agent, and (b) an absorption fabric which is soaked in or coated by an oral acceptable pre-modifier, wherein the oral treatment agent is an oral acceptable peroxide and the pre-modifier is an alkalizing agent or active agent of an oral care agent. The application also mentions γ-polyglutamic acid as one of the options for controlling calculus, calcium glycerol phosphate as one of the options for controlling dental plaque, and calcium phosphate as one of the abrasives. Nevertheless, it does not mention the combination of γ-PGA and calcium phosphate and the effects that it may produce.
Taiwan Patent Publication No. 200610544 discloses a composition for application to the tooth surface for delivering the oral treatment material. The composition is a flexible thin film, comprising an oral treatment material distributed in an effective amount and polymeric matrix film. The matrix has weight selected hydrophobic parts and hydrophilic parts to make the film substantially dissolvable in the saliva during oral treatment. The application also mentions γ-polyglutamic acid as one of the options for controlling calculus, and calcium glycerol phosphate as one of the options for controlling dental plaque. Nevertheless, it does not mention the combination of γ-PGA and calcium phosphate and the effects that it may produce.
Taiwan Patent Publication No. 200637605 discloses a toothpaste composition comprising a wetting agent, an abrasive, and an antibacterial component including ursolic acid and carnosic acid. The application also mentions γ-polyglutamic acid as one of the options for controlling calculus, and calcium phosphate as one of the options for controlling dental plaque. Nevertheless, it does not mention the combination of γ-PGA and calcium phosphate and the effects that it may produce.
Taiwan Patent Publication No. 200640531 discloses an oral care composition comprising one or more oregano extract active components in a safe and effective amount, and an oral acceptable carrier. The application also mentions γ-polyglutamic acid as one of the anti-calculus agents, and calcium glycerol phosphate as one of the anti-dental plaque agents. Nevertheless, it does not mention the combination of γ-PGA and calcium phosphate and the effects that it may produce.
Taiwan Patent Publication No. 200735895 discloses a particle comprising a core comprising oxide or its salt and a bio-adhered polymer, wherein the bio-adhered polymer is attached to the oxide or its salt. The application mentions that the bio-adhered polymer can be peptide and the oxide can be alkaline earth metal phosphate salt. Nevertheless, the focus is on the ability of the particle and the bio-adhered polymer to prevent bacteria from adhering or attaching to the fixing part. The application does not mention the combination of γ-PGA and calcium phosphate, let alone that such combination can decrease oral acidity, enhance adhesion of calcium ions to oral surfaces, and improve dental caries.
Taiwan Patent Publication No. 200738272 discloses a dental composition comprising an active dental material, at least one effective sweetener, and at least one sweet modifier. It can comprise an additional sweet modifier and an inorganic phosphate salt. Nevertheless, it does not mention the combination of γ-PGA and calcium phosphate and the effects that it may produce.
Taiwan Patent Publication No. 200806335 discloses a diphase whitening oral care composition comprising: (a) a first phase including a whitening agent that is substantially free of water and oral acceptable carrier, and (b) a second phase including an anti-calculus agent and abrasive, wherein the first phase and the second phase are separately placed before formulation. The application mentions calcium phosphate as one of the abrasives or polishing agents, and γ-PGA as one of the anti-calculus agents. Nevertheless, it does not mention the combination of γ-PGA and calcium phosphate and the effects that it may produce.
US 20050175959 provides a system for delivery of materials to the dental surfaces of an intraoral cavity to enable teeth repair. The application mentions that the active component includes calcium phosphate powder and γ-PGA colloid to aid teeth repair. Nevertheless, it does not specifically mention the combination of γ-PGA and calcium phosphate and the effects that it may produce. US 20090042161 provides a device for retention at dental sites within the intraoral cavity to enable the prevention of dental caries. Nevertheless, it does not mention the combination of γ-PGA and calcium phosphate and the effects that it may produce.
US 20030124066, US 20030152525 and U.S. Pat. No. 6,863,882 all provide an oral care composition, such as toothpaste. They mention that the composition includes a phosphopeptide-amorphous calcium phosphate complex and a calcium chelator for use in improving fluoride stability. Nevertheless, it does not specifically mention the combination of γ-PGA and calcium phosphate and the effects that it may produce. US 20080171001 also provides toothpaste including a phosphopeptide-amorphous calcium phosphate complex to enable the mineralization of teeth. Nevertheless, it does not mention the combination of γ-PGA and calcium phosphate and the effects that it may produce.
U.S. Pat. Nos. 5,837,674 and 6,306,822 are related to phosphopeptides used to reduce bone loss or weakening. U.S. Patent Publication Nos. 20060204580, 20040131562, 20030232071, 20060204581, 20050152990, and U.S. Pat. No. 7,455,854 are all related to a biomimetic of bone or a biomimetic hard tissue. US 20090035355 is related to agglomerates comprising calcium-hydrocolloid-composite materials to promote repair of tooth material. Nevertheless, they do not mention the combination of γ-PGA and calcium phosphate and the effects that it may produce.